CACNA1C and familial long QT syndrome: In this context, the LQTS phenotype associated with the glycine to arginine substitution in the I–II linker could result from either process: an intrinsically stronger activation of CaV1.2 that renders the channel insensitive to cellular variations in phosphorylated CaM or else a higher affinity to CaM that causes the channel to be maximally activated at near endogenous concentration of CaM.